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Introduction: Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited., Aim: To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age., Methods: Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression., Results: In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS., Conclusion: Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The role of air pollution in eczema and food allergy development remains understudied., Objective: We aimed to assess whether exposure to air pollution is associated with eczema and food allergies in the first 10 years of life., Methods: HealthNuts recruited a population-based sample of 1-year-old infants who were followed up at ages 4, 6, and 10 years. Annual average fine particulate matter (particulate matter with diameter of 2.5 μm or less, or PM 2.5 ) and nitrogen dioxide (NO 2 ) exposures were assigned to geocoded residential addresses. Eczema was defined by parent report. Oral food challenges to peanut, egg, and sesame were used to measure food allergy. Multilevel logistic regression models were fitted, and estimates were reported as adjusted odds ratios., Results: Those exposed to high concentration of NO 2 (<10 ppb) at age 1 year had higher peanut allergy prevalence at ages 1 (adjusted odds ratio [95% confidence interval], 2.21 [1.40-3.48]) and 4 (2.29 [1.28-4.11]) years. High exposure to NO 2 at 6 years old were associated with higher peanut allergy prevalence at age 6 (1.34 [1.00-1.82] per 2.7 ppb NO 2 increase) years. Similarly, increased PM 2.5 at age 1 year was associated with peanut allergy at ages 4, 6, and 10 years (respectively, 1.27 [1.01-1.60], 1.27 [1.01-1.56], and 1.46 [1.05-2.04] per 1.2 μg/m PM 2.5 increase) years. We found that increased concentrations of NO 2 or PM 2.5 at age 1 year were associated with persistent peanut allergy at later ages. Little evidence of associations was observed with eczema or with egg allergy., Conclusions: Early-life exposure to PM 2.5 and NO 2 was associated with peanut allergy prevalence and persistence. Policies aiming at reducing air pollution could potentially reduce presence and persistence of peanut allergy., Competing Interests: Disclosure statement Supported by funding from the National Health and Medical Research Council (NHMRC) of Australia, the Ilhan Food Allergy Foundation, AnaphylaxiStop, the Charles and Sylvia Viertel Medical Research Foundation, and the Victorian government’s Operational Infrastructure Support Program. R.P., C.L., K.P.P., and A.L. are supported by NHMRC awards. K.P.P. is also funded by a Melbourne Children’s Clinician-Scientist Fellowship. D.L. was supported by the University of Melbourne and Becas Carlos Antonio Lopez scholarship. The funding agencies had no direct role in the conduct of the study; the collection, management, statistical analysis, and interpretation of the data; decision to submit the report for publication; or the preparation and approval of the report. Disclosure of potential conflict of interest: C. J. Lodge, S. C. Dharmage, and A. J. Lowe have received research funds from GSK’s competitively awarded Investigator sponsored studies program for unrelated research. A. J. Lowe has received grant funding from SanofiRegeneron for unrelated research; and has received donations of interventional product (EpiCeram) from Primus Pharmaceuticals for unrelated research. J. C. Su has been consultant/speaker/investigator for AbbVie, Amgen, Bioderma, Bristol Myers Squibb, Ego Pharmaceuticals, Eli Lilly, Janssen, LEO Pharma, L’Oreal, Mayne, Novartis, Pfizer, Pierre-Fabre, and Sanofi. K. P. Perrett has received research grants from Aravax, DBV Technologies, Novartis, and Siolta; and consultant fees from Aravax, paid to Perrett’s institution, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: The term "pre-chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z -scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV 1 /FVC z -score less than -1.264, corresponding to the lowest 10 th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV 1 /FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV 1 /FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings.

Background: Cough is a common yet heterogeneous condition. Little is known about the characteristics and course of cough in general populations. We aimed to investigate cough subclasses, their characteristics from childhood across six decades of life, and potential treatable traits in a community-based cohort., Methods: For our analysis of the Tasmanian Longitudinal Health Study (TAHS), a prospective, community-based cohort study that began on Feb 23, 1968, and has so far followed up participants in Tasmania, Australia, at intervals of 10 years from a mean age of 7 years to a mean age of 53 years, we used data collected as part of the TAHS to distinguish cough subclasses among current coughers at age 53 years. For this analysis, participants who answered Yes to at least one cough-related question via self-report questionnaire were defined as current coughers and included in a latent class analysis of cough symptoms; participants who answered No to all nine cough-related questions were defined as non-coughers and excluded from this analysis. Two groups of longitudinal features were assessed from age 7 years to age 53 years: previously established longitudinal trajectories of FEV 1 , forced vital capacity [FVC], FEV 1 /FVC ratio, asthma, and allergies-identified via group-based trajectory analysis or latent class analysis-and symptoms at different timepoints, including asthma, current productive cough, ever chronic productive cough, current smoking, and second-hand smoking., Findings: Of 8583 participants included at baseline in the TAHS, 6128 (71·4%) were traced and invited to participate in a follow-up between Sept 3, 2012, and Nov 8, 2016; 3609 (58·9%) of these 6128 returned the cough questionnaire. The mean age of participants in this analysis was 53 years (SD 1·0). 2213 (61·3%) of 3609 participants were defined as current coughers and 1396 (38·7%) were categorised as non-coughers and excluded from the latent class analysis. 1148 (51·9%) of 2213 participants in this analysis were female and 1065 (48·1%) were male. Six distinct cough subclasses were identified: 206 (9·3%) of 2213 participants had minimal cough, 1189 (53·7%) had cough with colds only, 305 (13·8%) had cough with allergies, 213 (9·6%) had intermittent productive cough, 147 (6·6%) had chronic dry cough, and 153 (6·9%) had chronic productive cough. Compared with people with minimal cough, and in contrast to other cough subclasses, people in the chronic productive cough and intermittent productive cough subclasses had worse lung function trajectories (FEV 1 persistent low trajectory 2·9%, 6·4%, and 16·1%; p=0·0011, p<0·0001; FEV 1 /FVC early low-rapid decline trajectory 2·9%, 12·1%, and 13·0%; p=0·012, p=0·0007) and a higher prevalence of cough (age 53 years 0·0%, 32·4% [26·1-38·7], and 50·3% [42·5-58·2]) and asthma (age 53 years 6·3% [3·7-10·6], 26·9% [21·3-33·3], and 41·7% [24·1-49·7]) from age 7 years to age 53 years., Interpretation: We identified potential treatable traits for six cough subclasses (eg, asthma, allergies, and active and passive smoking for productive cough). The required management of productive cough in primary care (eg, routine spirometry) might differ from that of dry cough if our findings are supported by other studies. Future population-based studies could apply our framework to address the heterogeneity and complexity of cough in the community., Funding: The National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, Victorian Asthma Foundation, Queensland Asthma Foundation, Tasmanian Asthma Foundation, The Royal Hobart Hospital Research Foundation, the Helen MacPherson Smith Trust, GlaxoSmithKline, and the China Scholarship Council., Competing Interests: Declaration of interests SCD, CJL, AJL, DSB, MJA, and JLP have investigator-initiated grants from GlaxoSmithKline. SCD, AJL, and MJA have investigator-initiated grants from Sanofi. SCD, JLP, CJL, DSB, and ABC are supported by the National Health and Medical Research Council of Australia (NHMRC). JLP is financially supported by the Australian Asthma Foundation, Craig Clifford Medical Trust, Helen McPherson Trust, and GlaxoSmithKline. AJL has received non-financial, technical support from Primus Pharmaceuticals. ABC has investigator-initiated grants from the NHMRC and the Australian Medical Research Future Fund; is a member of a data safety monitoring committee for GlaxoSmithKline, AstraZeneca, and Moderna; and was on the NHMRC Health Impact Committee, NHMRC Women in Science, and the European Respiratory Society Guideline Committee. JLP and SCD have an investigator-initiated grant from AstraZeneca. MJA has investigator-initiated grants from Pfizer and Boehringer-Ingelheim, was a consultant for Sanofi, received a speaker's fee from GlaxoSmithKline, and is an honorary member of the independent data monitoring committee for the NHMRC-funded Vietnam COPD Asthma and Prevention of Smoking 4 Trial via the Woolcock Institute. JZ is supported by The University of Melbourne and the China Scholarship Council joint PhD scholarship. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults., Methods: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations., Results: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE., Conclusions: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence., Competing Interests: Competing interests: SD, CJL, MA, JP and AJL declare they have received research funds from GSK’s competitively awarded Investigator Sponsored Studies programme, for unrelated research. AJL, SD and MA have received grant funding from Sanofi Regeneron for unrelated research. SD has received funds from AZ for unrelated research. AJL has received donations of interventional product (EpiCeram) from Primus Pharmaceuticals for unrelated research. JCS has been a consultant/speaker/investigator for AbbVie, Amgen, Bioderma, Bristol Myers Squibb, Ego Pharmaceuticals, Eli-Lilly, Janssen, LEO Pharma, L’Oreal, Mayne, Novartis, Pfizer, Pierre-Fabre, and Sanofi. MA holds investigator-initiated grants for unrelated research from Pfizer, Boehringer-Ingelheim and Sanofi. MA has also undertaken an unrelated consultancy for Sanofi. MA has also received a speaker’s fee from GSK., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes., Methods: Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into "explained cough" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or "unexplained cough" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years., Results: The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being "unexplained". Participants with unexplained chronic cough had lower FEV 1 /FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough., Conclusions: Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research., Competing Interests: Conflicts of interest Michael Abramson received grants from Pfizer and Boehringer Ingelheim outside the submitted work. Other authors have no conflicts of interest., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background/objective: Obesity is a risk factor for multimorbidity, including depression and possibly anxiety. However, it is currently unclear how patterns of change in BMI over the life course differentially influence the magnitude in risk of depression and anxiety in mid-adulthood. We aimed to examine associations between BMI trajectories from childhood to adulthood and the risk of depression and anxiety in middle age., Methods: In the Tasmanian Longitudinal Health Study (n = 2416), five distinct BMI trajectories were previously defined from age 5 to 45 years using group-based modelling. At age 53, current depression and anxiety were assessed using the Patient Health Questionnaire and the Generalized Anxiety Disorder scale, respectively. Logistic regression models adjusted for potential confounders estimated associations between BMI trajectories and these outcomes., Results: Those belonging to the child average-increasing (OR = 2.24; 95%CI: 1.24, 4.06) and persistently high (OR = 2.64; 1.26, 5.52) trajectories were more likely to have depression in middle age, compared to the persistently average trajectory. However, the odds of experiencing greater severity of depressive symptoms was highest in the child average-increasing group (OR = 2.36; 1.59, 3.49). Despite finding no evidence of association between BMI trajectories and current anxiety, we observed less severe symptoms in the child high-decreasing trajectory (OR = 0.68; 0.51, 0.91)., Conclusion: We found an increased risk of depression in middle age among individuals with a persistently high BMI from childhood to mid-adulthood and individuals with an average BMI in childhood which then increased consistently throughout adulthood. Encouragingly, resolving childhood adiposity by adulthood was associated with lesser anxiety symptoms. Taken together, these findings highlight the need to target mental health screening and treatment towards high-risk BMI trajectory groups and the importance of early interventions to prevent and resolve excess weight., (© 2023. The Author(s).)

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.

There is current interest in the role of ambient pollen in the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19) infection risk. The aim of this review is to summarise studies published up until January 2023 investigating the relationship between airborne pollen and the risk of COVID-19 infection. We found conflicting evidence, with some studies showing that pollen may increase the risk of COVID-19 infection by acting as a carrier, while others showed that pollen may reduce the risk by acting as an inhibiting factor. A few studies reported no evidence of an association between pollen and the risk of infection. A major limiting factor of this research is not being able to determine whether pollen contributed to the susceptibility to infection or just the expression of symptoms. Hence, more research is needed to better understand this highly complex relationship. Future investigations should consider individual and sociodemographic factors as potential effect modifiers when investigating these associations. This knowledge will help to identify targeted interventions.

Background: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub-clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline., Methods: The Tasmanian Longitudinal Health Study is a population-based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re-evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed., Results: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2-high (42%) and Th2-low (24%). Compared to the average profile, a Th2-high profile was associated with accelerated decline in post-BD FEV 1 /FVC (MD -0.18% predicted per-year; 95% CI -0.33, -0.02), while a Th2-low profile was associated with accelerated decline in both post-BD FEV 1 (-0.41%; -0.75, -0.06) and post-BD FVC (-0.31%; -0.62, 0.01). BHR and high TNF-α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline., Conclusion: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At-risk individuals with BHR, Th2-high or Th2-low cytokine profiles may benefit from closer monitoring and on-going follow-up., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV 1 /forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups., Methods: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV 1 /FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV 1 /FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated., Findings: The prevalence of the four lifetime spirometry patterns was as follows: low FEV 1 /FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV 1 /FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV 1 /FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea., Interpretation: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV 1 /FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age., Funding: National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline., Competing Interests: Declaration of interests CJL, EHW, AJL, DSB, MJA, JLP, and SCD hold an investigator-initiated grant from GlaxoSmithKline for unrelated research. SCD holds an investigator-initiated grant from AstraZeneca for unrelated research. MJA holds investigator-initiated grants from Pfizer, Boehringer Ingelheim, and Sanofi for unrelated research; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and received speaker's fees from GlaxoSmithKline. AJL has received non-financial support from Primus Pharmaceuticals for unrelated research. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objective: The association between birth weight, particularly relative to gestational age, and adult lung function is uncertain. We investigated the associations between birth weight relative to gestational age and measures of lung function in middle age, and mediation of these associations by adult height., Methods: Participants in the Tasmanian Longitudinal Health Study who had both known birth weight and lung function assessment at age 45 years were included (n = 849). Linear regression models were fitted to investigate the association between small for gestational age and birth weight with post-bronchodilator lung function measures (forced expiratory volume in 1 second [FEV 1 ], forced vital capacity [FVC], FEV 1 /FVC, diffusing capacity for carbon monoxide [D L co], residual volume [RV] and total lung capacity [TLC]), adjusting for potential confounders. The contribution of adult height as a mediator of these associations was investigated., Results: Compared with infants born with normal weight for gestational age, those born small for gestational age had reduced FEV 1 (coefficient: -191 ml [95%CI: -296, -87]), FVC (-205 ml [-330, -81]), TLC (-292 ml [-492, -92]), RV (-126 ml [-253, 0]) and D L co (-0.42 mmol/min/kPa [-0.79, -0.041]) at age 45 years. However, they had comparable FEV 1 /FVC. For every 1 kg increase in birth weight, lung function indices increased by an average of 117 ml (95%CI: 40, 196) for FEV 1 , 124 ml (30, 218) for FVC, 215 ml (66, 365) for TLC and 0.36 mmol/min/kPa (0.11, 0.62) for D L co, independent of gestational age, but again not for FEV 1 /FVC. These associations were significantly mediated by adult height (56%-90%)., Conclusion: Small for gestational age was associated with reduced lung function that is likely due to smaller lungs with little evidence of any specific parenchymal impairment., (© 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Competing Interests: None.

Background: Eczema is a chronic inflammatory skin disease. Domestic water with high mineral content (hard water) is a risk factor for eczema in children, but this association has not been assessed in adults., Objectives: To examine the association between domestic hard water supply and eczema prevalence and incidence in adults aged 40-69 years and the contextual effect in eczema outcomes by postcode in adults in the UK., Methods: We used data from the UK Biobank study collected in 2006-10 (baseline) and 2013-14 (follow-up). Eczema prevalence at baseline (2006-10) and at follow-up (2013-14) and incidence (new onset between baseline and follow-up) were determined from the touchscreen questionnaires and nurse-led interviews. Domestic hard water information was obtained in 2005 and 2013 from the local water supply companies in England, Wales and Scotland as CaCO 3 concentrations. We fitted multilevel logistic regression models with random intercepts for postcode areas to examine the effect of domestic hard water on eczema outcomes, and we measured components of variance., Results: In total, 306 531 participants with a mean age of 57 years nested across 7642 postcodes were included in the baseline analysis, and 31 036 participants nested across 3695 postcodes were included in the follow-up analysis. We observed an increase in the odds of eczema at baseline [odds ratio (OR) 1·02, 95% confidence interval (CI) 1·01-1·04] per 50 mg L -1 of CaCO 3 increase. Furthermore, exposure to domestic hard water (> 200 mg L -1 of CaCO 3 ) was associated with increased odds of prevalent eczema at baseline (OR 1·12, 95% CI 1·04-1·22). Moreover, there was a significant linear trend (P < 0·001) in which increasing levels of hard water increased eczema prevalence risk. No association was observed with incident eczema or eczema at follow-up. The intraclass correlation coefficient for postcode was 1·6% (95% CI 0·7-3·4), which remained unexplained by area-level socioeconomic measures., Conclusions: Increasing levels of domestic hard water, as measured by CaCO 3 concentrations, were associated with an increased prevalence of eczema in adults but not increased incidence. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing the burden of eczema in adults. Further research is needed to explore area-level factors that may lead to eczema. What is already known about this topic? Hard water is formed when minerals are dissolved in water from filtration through sedimentary rocks. Several studies have reported a higher prevalence of eczema in areas with hard water. However, all studies on this topic have assessed this in infants and school-aged children, while this association has not been explored in adults. What does this study add? Our findings suggest that exposure to higher concentrations of domestic hard water is associated with an increase in eczema prevalence in adults aged 40-69 years. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing eczema prevalence in adults., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: High body mass index (BMI) trajectories from childhood to adulthood are associated with the development of some chronic diseases, but whether such trajectories influence adult asthma has not been investigated to date. Therefore, we investigated associations between BMI trajectories from childhood to middle age (5-43 years) and incidence, persistence and relapse of asthma from ages 43 to 53 years., Methods: In the Tasmanian Longitudinal Health Study (n=4194), weight and height were recorded at eight time-points between 5 and 43 years of age. BMI trajectories were developed using group-based trajectory modelling. Associations between BMI trajectories and asthma incidence, persistence and relapse from age 43 to 53 years, bronchial hyperresponsiveness (BHR) at age 50 years, and bronchodilator responsiveness at age 53 years were modelled using multiple logistic and linear regression., Results: Five distinct BMI trajectories were identified: average, low, child high-decreasing, child average-increasing and high. Compared with the average trajectory, child average-increasing and high trajectories were associated with increased risk of incident asthma (OR 2.6, 95% CI 1.1-6.6 and OR 4.4, 95% CI 1.7-11.4, respectively) and BHR in middle age (OR 2.9, 95% CI 1.1-7.5 and OR 3.5, 95% CI 1.1-11.4, respectively). No associations were observed for asthma persistence or relapse., Conclusions: Participants with child average-increasing and high BMI trajectories from childhood to middle age were at higher risk of incident adult asthma. Thus, encouraging individuals to maintain a normal BMI over the life course may help reduce the burden of adult asthma., Competing Interests: Conflicts of interest: M.J. Abramson holds investigator-initiated grants for unrelated research from Pfizer, Boehringer Ingelheim and Sanofi; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and has also received a speaker's fee from GSK. The other authors included in this study declare that they have no competing interests. All authors declare no support from any organisation or no financial relationship with any organisation that could appear to have influenced the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: The heterogeneity of development and progression of eczema suggests multiple underlying subclasses for which aetiology and prognosis may vary. A better understanding may provide a comprehensive overview of eczema development and progression in childhood. Thus, we aimed to determine longitudinal eczema subclasses based on assessments and identify their associations with risk factors and allergic outcomes., Methods: A total of 619 participants with a family history of allergic disease were assessed at 24 time-points from birth to 12 years. At each time, eczema was defined as the report of current rash treated with topical steroid-based preparations. Longitudinal latent class analysis was used to determine eczema subclasses. Subsequent analyses using regression models assessed the associations between eczema subclasses and potential risk factors and allergic outcomes at 18- and 25-year follow-ups (eczema, allergic rhinitis, asthma and allergic sensitization)., Results: We identified five eczema subclasses 'early-onset persistent', 'early-onset resolving', 'mid-onset persistent', 'mid-onset resolving' and 'minimal eczema'. Filaggrin null mutations were associated with the early-onset persistent (OR = 2.58 [1.09-6.08]) and mid-onset persistent class (OR = 2.58 [1.32-5.06]). Compared with 'minimal eczema', participants from early-onset persistent class had higher odds of eczema (OR = 11.8 [5.20-26.6]) and allergic rhinitis (OR = 3.13 [1.43-6.85]) at 18 and at 25 years eczema (OR = 9.37 [3.17-27.65]), allergic rhinitis (OR = 3.26 [1.07-9.93]) and asthma (OR = 2.91 [1.14-7.43]). Likewise, mid-onset persistent class had higher odds of eczema (OR = 2.59 [1.31-5.14]), allergic rhinitis (OR = 1.70 [1.00-2.89]) and asthma (OR = 2.00 [1.10-3.63]) at 18 and at 25 years eczema (OR = 6.75 [3.11-14-65]), allergic rhinitis (OR = 2.74 [1.28-5.88]) and asthma (OR = 2.50 [1.25-5.00]). Allergic and food sensitization in early life was more common in those in the persistent eczema subclasses., Conclusion: We identified five distinct eczema subclasses. These classes were differentially associated with risk factors, suggesting differences in aetiology, and also with the development of allergic outcomes, highlighting their potential to identify high-risk groups for close monitoring and intervention., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Recent evidence suggests that parental exposures before conception can increase the risk of asthma in offspring., Objective: We investigated the association between parents' preconception body mass index (BMI) trajectories from childhood to adolescence and subsequent risk of asthma in their offspring., Methods: Using group-based trajectory modeling from the Tasmanian Longitudinal Health Study, we identified BMI trajectories for index participants (parents) when aged 4 years to 15 years. Multinomial regression models adjusted for potential confounders were utilized to estimate the association between these early-life parents' BMI trajectories and asthma phenotypes in their subsequent offspring., Results: The main analysis included 1822 parents and 4208 offspring. Four BMI trajectories from age 4 years to 15 years were identified as the best-fitting model: low (8.8%), normal (44.1%), above normal (40.2%), and high (7.0%). Associations were observed between father's high BMI trajectory and risk of asthma in offspring before the age of 10 years (relative risk ratio [RRR] =1.70 [95% CI = 0.98-2.93]) and also asthma ever (RRR = 1.72 [95% CI = 1.00-2.97]), especially allergic asthma ever (RRR = 2.05 [95% CI = 1.12-3.72]). These associations were not mediated by offspring birth weight. No associations were observed for maternal BMI trajectories and offspring asthma phenotypes., Conclusion: This cohort study over 6 decades of life and across 2 generations suggests that the high BMI trajectory in fathers, well before conception, increased the risk of asthma in their offspring., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Respiratory diseases such as asthma, allergic rhinitis (AR) and chronic obstructive pulmonary disease (COPD) affect millions worldwide and pose a significant global public health burden. Over the years, changes in land use and climate have increased pollen quantity, allergenicity and duration of the pollen season, thus increasing its impact on respiratory disease. Many studies have investigated the associations between short-term ambient pollen (i.e., within days or weeks of exposure) and respiratory outcomes. Here, we reviewed the current evidence on the association between short-term outdoor pollen exposure and thunderstorm asthma (TA), asthma and COPD hospital presentations, general practice (GP) consultations, self-reported respiratory symptoms, lung function changes and their potential effect modifiers. The literature suggests strong evidence of an association between ambient pollen concentrations and almost all respiratory outcomes mentioned above, especially in people with pre-existing respiratory diseases. However, the evidence on sub-clinical lung function changes, COPD, and effect modifiers other than asthma, hay fever and pollen sensitisation are still scarce and requires further exploration. Better understanding of the implications of pollen on respiratory health can aid healthcare professionals to implement appropriate management strategies.

Background: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown., Objective: To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age., Design: Cohort study from age 7 to 53 years., Setting: General population of European descent from Tasmania, Australia., Participants: 3202 participants of the age 53-year follow-up (mean age 53, range 51-55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis., Statistical Methods: Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated., Results: Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: 'non-recurrent bronchitis' (28.1%); 'recurrent non-protracted bronchitis' (18.1%) and 'recurrent-protracted bronchitis' (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend <0.001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, 'recurrent-protracted bronchitis' (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15-0.88)), when compared with no childhood bronchitis., Conclusion: In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. 'Recurrent-protracted bronchitis', while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood 'bronchitis' into middle-age., Competing Interests: Competing interests: JP, AL, CL, DB, EHW, MJA and SCD have received an investigator-initiated grant from GlaxoSmithKline for unrelated research, and SCD holds a similar grant from AstraZeneca. MJA also holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim and Sanofi for unrelated research; has undertaken an unrelated consultancy and received assistance with conference attendance from Sanofi; and received a speaker’s fee from GlaxoSmithKline. ABC is on independent data safety and monitoring boards for a SARs-COV2 vaccine (Moderna), an unlicensed RSV vaccine (GSK) and monoclonal antibody (AstraZeneca), where the monies are received by her institution. BRT serves on the medical advisory boards of Chiesi Australia and 4D Medical and has received an unrelated consultancy from GlaxoSmithKline and speaker fees from Mundipharma. AL has received investigational product (EpiCeram TM) free of charge from Primus Pharmaceuticals for use in unrelated research. DW has received consultancy fee from MSD for participation on an expert input forum, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS)., Methods: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV 1 , forced vital capacity [FVC], FEV 1 /FVC ratio, forced expiratory flow at 25-75% of FVC [FEF 25-75% ], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV 1 /FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated., Results: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV 1 /FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV 1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF 25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV 1 /FVC ratio was only significant among smokers (p interaction =0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV 1 /FVC ratio or COPD., Interpretation: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking., Funding: National Health and Medical Research Council (NHMRC) of Australia, European Union's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline., Competing Interests: Declaration of interests DSB, JLP, MJA, EHW, AJL, CJL, and SCD hold an investigator-initiated grant from GlaxoSmithKline for unrelated research. SCD holds an investigator-initiated grant from AstraZeneca for unrelated research. MJA holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim, and Sanofi for unrelated research; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and received a speaker's fee from GlaxoSmithKline. BRT has received unrelated speaker and consultancy fees from Chiesi, Mundipharma, and 4D medical. AJL has received non-financial support from Primus Pharmaceuticals for unrelated research. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Early life body mass index (BMI) trajectories influence the risk of asthma at 18 years of age. However, it is unclear if these are also associated with other allergic diseases., Objectives: We investigated the associations between BMI trajectories and subsequent allergic rhinitis, eczema and food sensitisation/allergies., Methods: Parent-reported anthropometric data were collected 18 times in the first two years of life from a cohort of 620 participants in a high-risk cohort. Group-based trajectory modelling was applied to develop BMI trajectories. Associations between trajectories and allergic rhinitis, eczema and food sensitisation at 6, 12 and 18 years of age were assessed using logistic regression models. Potential effect modifications by parental allergic disease, sex and allocated infant formula were assessed., Results: We identified five BMI trajectories: average, below average, persistently low, early low and catch up, and persistently high. None showed an association with allergic rhinitis. In participants with maternal allergic rhinitis, 'early-low and catch-up' (OR = 2.83;95%CI 1.34-5.96, P int  = 0.05) and 'below average' trajectories (OR = 2.39; 1.18-7.23, P int  = 0.02) were associated with allergic rhinitis at 18 years of age compared with the average trajectory. No associations were observed with eczema or food sensitisation., Conclusion: Infants with early-low and catch-up, or below average BMI growth, were at increased risk of allergic rhinitis at 18 years if they had a mother with allergic rhinitis. These results require replication, but suggest that interactions between poor intrauterine growth, failure to thrive and maternal allergies may influence the risk of allergic rhinitis., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Despite the challenges of diagnosing and managing adult patients with chronic cough, a systematic synthesis of evidence on aetiological risk factor is lacking. We systematically searched PubMed and EMBASE to synthesize the current evidence for longitudinal associations between a wide range of risk factors and chronic cough in the general adult population, following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Fixed-effect meta-analysis was conducted where appropriate. Of 26 eligible articles, 16 domains of risk factors were assessed. There was consistent evidence that asthma (pooled adjusted OR [aOR] = 3.01; 95% CI: 2.33-3.70; I 2  = 0%; number of articles [N] = 3) and low education levels/socioeconomic status (SES) (pooled aOR = 1.46; 95% CI: 1.20-1.72; I 2  = 0%; N = 3) were associated with an increased risk of chronic cough after adjusting for smoking and other confounders. While continuous smoking was associated with chronic cough (aOR = 1.81; 95% CI: 1.36-2.26; I 2  = 57%; N = 3), there was too little evidence to draw conclusions for occupational exposures, outdoor air pollution, early-life exposures, diet, snoring and other chronic conditions, including obesity, chronic obstructive pulmonary disease, gastro-oesophageal reflux disease and chronic pain. Asthma, persistent smoking and lower education/SES were associated with an increased risk of chronic cough. Longitudinal associations between other factors frequently mentioned empirically (i.e., occupational exposures, air pollution and chronic respiratory conditions) need further investigation, ideally with objective and standardized measurement., (© 2021 Asian Pacific Society of Respirology.)

Background: Classifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention., Objective: To develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile)., Setting: General Caucasian populations from Australia and Europe, 10 and 27 centres, respectively., Participants: For the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41-45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51-55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40-49 and 50-59 with complete questionnaire and spirometry/smoking data, respectively (n=1407)., Statistical Method: Risk-prediction models were developed using randomForest then externally validated., Results: Area under the receiver operating characteristic curve (AUC ROC ) of the final model was 80.8% (95% CI 80.0% to 81.6%), sensitivity 80.3% (77.7% to 82.9%), specificity 69.1% (68.7% to 69.5%), positive predictive value (PPV) 11.1% (10.3% to 11.9%) and negative predictive value (NPV) 98.7% (98.5% to 98.9%). The external validation was fair (AUC ROC 75.6%), with the PPV increasing to 17.9% and NPV still 97.5% for adults aged 40-49 years with ≥1 respiratory symptom. To illustrate the model output using hypothetical case scenarios, a 43-year-old female unskilled worker who smoked 20 cigarettes/day for 30 years had a 27% predicted probability for post-BD-AO at age 53 if she continued to smoke. The predicted risk was 42% if she had coexistent active asthma, but only 4.5% if she had quit after age 43., Conclusion: This novel and validated risk-prediction model could identify adults aged in their 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted 'COPD cases' at a much earlier age., Competing Interests: Competing interests: JP received a travel grant supported by Boehringer-Ingelheim, and together with MJA, EHW, AL, CL and SCD, holds an investigator-initiated grant from GlaxoSmithKline for unrelated research. SCD additionally holds an investigator-initiated grant from AstraZeneca for unrelated research. MJA also holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim and Sanofi for unrelated research; has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi; and received a speaker’s fee from GlaxoSmithKline. BRT has received unrelated speaker and consultancy fees from Chiesi, Mundipharma and 4D medical. KH has received personal fees and non-financial support from Astra Zeneca, GlaxoSmithKline, Novartis, Chiesi, Boehringer Ingelheim and Teva outside the submitted work. AL has additionally received non-financial support from Primus Pharmaceuticals for unrelated research. No other authors reported financial disclosures., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The relationship between asthma and coronavirus disease 2019 (COVID-19) risk is not clear and may be influenced by level of airway obstruction, asthma medication and known COVID-19 risk factors. We aimed to investigate COVID-19 risk in people with asthma., Methods: We used UK Biobank data from all participants tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=107 412; 17 979 test positive). Questions at baseline defined ever asthma and asthma medications. Baseline forced expiratory volume in 1 s (FEV 1 ) was categorised into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV 1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking and body mass index., Results: There was a reduced risk of a positive test associated with early-onset asthma (<13 years) (OR 0.91, 95% CI 0.84-0.99). This was found for participants with early-onset asthma who were male (OR 0.87, 95% CI 0.78-0.98), nonsmokers (OR 0.87, 95% CI 0.78-0.98), overweight/obese (OR 0.85, 95% CI 0.77-0.93) and non-Black (OR 0.90, 95% CI 0.82-0.98). There was increased risk amongst early-onset individuals with asthma in the highest compared to lowest quartile of lung function (1.44, 1.05-1.72)., Conclusion: Amongst male, nonsmoking, overweight/obese and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Individuals with early-onset asthma of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks., Competing Interests: Provenance: Submitted article, peer reviewed. Conflict of Interest: C.J. Lodge, D.S. Bui, R. Cassim, A.J. Lowe and S.C. Dharmage are investigators on a GlaxoSmithKline grant that is unrelated to and had no influence on this work. A. Doherty has nothing to disclose. Conflict of interest: A.J. Lowe reports receiving Research Fellowships from National Health and Medical Research Council, during the conduct of the study. Conflict of interest: A. Agusti has nothing to disclose. Conflict of interest: M.A. Russell has nothing to disclose., (Copyright ©The authors 2021.)